Adverse ocular effects of neuroleptic therapy: semiotics, pathogenesis and treatment

Antipsychotics are widely used in psychiatric practice for treating schizophrenia, bipolar disorder, and other diseases, including those treated off-label. They manifest many adverse effects, including ophthalmic ones. Some of these effects, such as persistent mydriasis, cycloplegia, extraocular muscle dystonia, and visual hypersensitivity attacks are reversible, since they disappear after dose reduction or drug withdrawal. Yet other side effects, such as cataracts, corneal edema, acute angle closure glaucoma and retinopathy are threatening for sight and may lead to permanent visual acuity decline and even blindness. The review provides data on the incidence of ocular side effects (both typical and atypical) of multiple antipsychotics, their clinical manifestations, pathogenesis and treatment. Eye examination is recommended for patients taking antipsychotics in the early periods of treatment and then twice a year. The psychiatrists need to know about the adverse effects of individual drugs whilst the ophthalmologists should be aware of their semiotics, pathogenesis and treatment, since timely diagnosis and treatment of pathological changes, together with antipsychotic therapy modification, prevent the development of severe and irreversible visual impairment in the majority of cases.

Potential drug interactions analysis of COVID-19 patients at a hospital in West Java

Background: Treatment guidelines of COVID-19 are changing continuously by involving many off-label and various symptomatic or supportive drugs. The use of these various drugs might increase the patient’s risk of developing drug interactions. Objective: The study aimed to analyze potential drug-drug interactions in COVID-19 inpatients and the correlated factors. Method: A cross-sectional study was conducted in a hospital by using inpatients admitted from August-December 2020. Potential drug-drug interaction was analyzed by using Lex-Interact® software. Results: From 107 patients, the majority of them are in moderate severity-degree (98.1%), having comorbidities (93.5%), and polypharmacy (98.1%). The average of potential drug interactions was 8.47±8,04, with most of the interaction in risk rating C-monitor therapy. Major potential drug interactions found were prolongation of QT interval and disturbance of drug absorption in the gastrointestinal tract. A positive correlation occurred between drug interactions found and comorbidity (r=0.436), number of drugs per prescription (r=0.674), and length of stay (r=0.222) Conclusions: COVID-19 patient is at risk for developing potential drug interactions that can affect the patient's physiological condition and reduce drug effect. It is necessary to manage the medication schedule, therapy modification, administration route changing, dosage adjustment, and monitoring of effects that might occur because of the drug interactions. Keywords: drug interaction, COVID-19, inpatient, correlated factor

Time to modification of antiparkinson therapy in a group of patients from Colombia v1

Aims:To determine the time elapsed between the start of treatment with antiparkinson agents and the modification of the pharmacological therapy, and to establish its related factors, in a group of patients with Parkinson's disease from Colombia. Methods: Retrospective cohort study that collected information about the treatment of patients with Parkinson's disease who started drug therapy between June-2011 and December-2013; a 5-year follow-up was performed. Survival analyses for time to therapy modification were generated, and factors related to these changes were determined using Cox regression models. Results: A total of 3,224 patients (51.8% men) with a mean age of 73.1 ± 13.5 years started treatment with antiparkinson agents. After 5 years, 2,046 patients (63.5%) had modifications in drug therapy, in a mean time of 36.4 months (95% CI: 35.7-37.1). A total of 1,216 patients (37.8%) required the addition of another active principle, while 830 (25.7%) had a switch to another drug. In the multivariate analysis, male gender, age over 65 years, and the start of amantadine were identified as factors that increased the likelihood of therapy modification. The use of bromocriptine, biperiden, and monotherapy as an initial treatment were associated with a reduction in this likelihood. Conclusions: After 5 years of treatment, 63.5% of the patients with Parkinson's disease required modifications of their therapy, with a mean time of 3 years. Male sex, age over 65 years, and receiving initial therapy with amantadine affected the likelihood of switching therapy in these patients in Colombia.

The impact of curative treatment on hyperglycemia in patients with Cushing syndrome

Context Hyperglycemia is a common complication of Cushing syndrome (CS). Objective We aimed to determine the impact of curative procedure on hyperglycemia and its management in patients with CS. Design Retrospective longitudinal cohort study, 2000-2019. Setting Referral center. Patients Adults with endogenous CS and hyperglycemia. Main outcome measure Hemoglobin A1c (HbA1c), intensity of hyperglycemia therapy, improvement of hyperglycemia. Results In 174 patients with CS (pituitary in 106, ectopic in 25, adrenal in 43), baseline median HbA1c was 6.9% (range 4.9-13.1), with 41 (24%) patients not on any therapy for hyperglycemia, 93 (52%) on oral medications, and 64 (37%) on insulin (median daily units of 58, range 10-360). Following CS remission, at the end of follow up (median 10.5 months), 37 (21%) patients demonstrated resolution of hyperglycemia, 82 (47%) demonstrated improvement, and 55 (32%) had no change or worsening in hyperglycemia. At the end of follow up, HbA1c decreased by 0.84% (p < 0.0001) and daily insulin dose decreased by a mean of 30 units, p < 0.0001. Biochemical hypercortisolism severity score (severe vs moderate/mild: Odds ratio (OR) of 2.4 (95%CI of 1.1-4.9)), and CS subtype (nonadrenal vs adrenal: OR of 2.9 (95%CI 1.3-6.4)), but not type of hyperglycemia (diabetes vs prediabetes: OR of 2.1 (0.9-4.9)) were associated with hyperglycemia improvement at the end of follow up. Conclusion Two thirds of patients with CS and hyperglycemia demonstrate resolution or improvement of hyperglycemia after a curative procedure. Close monitoring during CS recovery is needed to assure appropriate therapy modification.

Analysis of Direct Oral Anticoagulant Therapy With Concomitant Use of Interacting Antiretroviral Agents

Background: A theoretical interaction exists between human immunodeficiency virus (HIV) antiretroviral (ARV) agents and direct oral anticoagulants (DOACs), although the clinical significance is unclear. Objective: This study aimed to assess characteristics, prescribing patterns, and outcomes associated with concomitant therapy. Methods: A single-center, retrospective review was performed on patients older than 18 years prescribed a DOAC for any indication with concurrent interacting ARV(s) from June 2016 through June 2019. The primary endpoint was to assess prescribing and population characteristics. Secondary endpoints were to evaluate safety outcomes, DOAC level monitoring, readmissions, outpatient follow-up, and DOAC modification interventions. Results: Thirty-six patients (72 hospital admissions) were identified. The most common DOAC was apixaban (83.3%) and ARV was ritonavir (50%). Of the 72 encounters, 26 (36.1%) DOACs were dosed appropriately per guideline recommendations. Twenty pharmacy interventions for therapy modification were recognized. Eleven (30.6%) patients experienced bleeding and 2 (5.6%) thrombosis. Of the adverse events, all patients had renal impairment. Conclusions: As DOAC utilization grows, increasing use in HIV could be expected. More frequent adjustment or avoidance is recommended per guidelines. Our data suggest the majority of patients receive CYP3A4-inhibiting regimens. Caution should be employed with renal insufficiencies. Further studies are warranted to assess safety and efficacy within this population.

Title: REAL CLINICAL IMPACT OF DRUG-DRUG INTERACTIONS OF IM-MUNOSUPPRESSANTS IN TRANSPLANT PATIENTS

Aim: The main objective of this study was to determine the prevalence of real DDIs between immunosuppressants and other drugs in transplant patients. Methods: We conducted a prospective, observational 1-year study at a tertiary hospital, including all transplanted patients. We evaluated data from monitoring blood concentrations of immunosuppressive drugs and adverse drug events (ADEs) caused by DDIs. The DDIs were classified as C, D, or X according to their Lexi-Interact rating (C = monitor therapy, D = consider therapy modification, X = avoid combination). The clinical importance of real DDIs was expressed in terms of patient outcomes. The data were analyzed using Statistical Package for Social Sciences (SPSS) package v. 25.0 (IBM Corp., Armonk, NY, USA). Results: A total of 309 transplant patients were included. Their mean age was 52.0 ± 14.7 years (18–79) and 69.9% were male. The prevalence of real DDIs was 21.7%. Immunosuppressive drugs administered with anti-fungal azoles and tacrolimus (TAC) with nifedipine have a great clinical impact. Real DDIs caused ADEs in 22 patients. The most common clinical outcome was nephrotoxicity (1.6%; n=5), followed by hypertension (1.3%; n=4). Suggestions for avoiding category D and X DDIs included: changing the immunosuppressant dosage, using paracetamol instead of non-steroidal anti-inflammatory drugs, and interrupting atorvastatin. The number of drugs prescribed and having been prescribed TAC was associated with an increased risk of real DDIs. Conclusion: There are many potential DDIs described in the literature but only a small percentage proved to be real DDIs, based on the patients´ outcomes.

Antimicrobial resistance and antimicrobial therapy modification during COVID19 pandemic in large tertiary hospital

Objective. assessment of the evolution of the microbiological landscape of the hospital for the period of operation in 2020 into a pandemic of a new coronavirus infection in various departments, including intensive care units; change depending on the results of antibacterial therapy regimens. Materials and Methods. In a retrospective study, conducted from June to December 2020, in a multidisciplinary hospital working with COVID-19 infection, the resistance of isolated strains of microorganisms was analyzed in patients of different age groups. Resistance was assessed with test points in June and November 2020; depending on this, proposals were made to correct the internal (local) protocols of antimicrobial therapy. Results. The need for frequent and regular microbiological monitoring was confirmed. Further, we understood that the territories of the main and temporary hospital of the City Clinical Hospital No. 40 are heterogeneous and there are obvious differences both in structure and in the level of sensitivity. “In practice, these are two different hospitals”. Within the territories, the branches also differ from each other. When analyzing resistance in ICUs, it was revealed that within each hospital in each department, albeit similar in structure and profile of patients, there is a different level of resistance of strains. Conclusions. The structure of sensitivity generally corresponds to the world data, but for some pathogens it differs significantly. Microbiological monitoring should be carried out not only inside the hospital, but also inside the department. The increase in consumption of carbapenems and protected cephalosporins requires a reassessment of the practice of using AMP in any covid hospital, due to the impact on the epidemic situation both in the ICUs and in the hospital.

Remote Team-work Management of NORSE During the COVID-19 Lock-down

New-Onset Refractory Status Epilepticus (NORSE) is rare condition and sharing knowledge is vital in its management, based on strict collaboration between multiple specialists, continuous EEG (c-EEG) monitoring and prompt therapy modification. The COVID-19 pandemic challenged many of these established practices, due to “social distancing” measures, making it necessary to work around physical restrictions. We report a case of a 10-year-old with NORSE, admitted in a Paediatric Intensive-Care Unit and monitored with c-EEG and amplitude-integrated-EEG. The monitoring interface was live-streamed using video-conference web-based platforms allowing remote viewing. Multiple daily web-meetings took place between team members, where real-time therapy response was evaluated and confronted with medium-term trends in the epileptic activity, dictating further treatment and diagnostic steps. In addition to the known use of telemedicine in chronic conditions, we report how its use can be exploited to treat urgent conditions such as NORSE. By taking advantage of new tools and virtual environments, we were able to share treatment and diagnostic decisions and guarantee real-time therapy adjustments and a coherent course in treatment despite restrictions necessary for the COVID-19 pandemic. The constant specialist monitoring and the coherent and on-time communication of the patient’s condition relieved the family stress, usually complained in these situations.

183. Optimization of an Outpatient Antimicrobial Stewardship Process for Patients Discharged from the Emergency Department at an Academic Medical Center

Background Suboptimal antimicrobial therapy has resulted in the emergence of multi-drug resistant organisms. The objective of this study was to optimize the time to antimicrobial therapy modification for patients discharged from the emergency department (ED) of an academic medical center through implementation of a pharmacist-driven outpatient antimicrobial stewardship initiative (ASI). Methods This was a pre-post, quasi-experimental study that evaluated the impact of a pharmacist-driven outpatient antimicrobial stewardship initiative at a single academic medical center. The pre-cohort was evaluated through manual electronic medical record (EMR) review, while the post-cohort involved a real-time notification alert system through an electronic clinical surveillance application. The difference in time from positive culture result to antimicrobial therapy optimization before and after implementation of the pharmacist-driven ASI was collected and analyzed. Results A total of 166 cultures were included in the analysis. Of these, 12/72 (16%) in the pre-cohort and 11/94 (12%) in the post-cohort required antimicrobial therapy modification, with a 21.9-hour reduction in median time from positive culture result to antimicrobial optimization in the post-cohort (43 h vs. 21.1 h; p < 0.01). Similarly, the median time from positive culture result to review was reduced by 20 hours with pharmacist-driven intervention (21.1 h vs. 1.4 h; p < 0.01). Conclusion The implementation of a pharmacist-driven outpatient antimicrobial stewardship initiative resulted in a significant reduction in time to positive culture review and therapy optimization for patients discharged from the ED of an academic medical center set in Philadelphia, PA. Disclosures All Authors: No reported disclosures